Editors' ChoiceDiabetes

Another Step Toward a Cure for Type 1 Diabetes Mellitus

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Science Translational Medicine  25 Aug 2010:
Vol. 2, Issue 46, pp. 46ec132
DOI: 10.1126/scitranslmed.3001601

The immune cells of almost 2 million people in the United States attack and destroy their own insulin-producing β cells of the pancreas. Left with life-long type 1 diabetes mellitus (T1DM), these people are treated with replacement insulin—a life-saving, albeit cumbersome, therapy. Nonetheless, a cure for T1DM remains a scientific “holy grail.” To identify an alternative treatment, Jörns et al. have investigated an agent that modifies the immune system in a way that may prevent the development of T1DM.

FTY720 is an established drug used for the prevention of organ rejection after transplantation. It maintains the B and T immune cells in a dormant state by potently binding to the sphingosine 1-phosphate receptor–1 (S1P1). In animal models of diabetes and prediabetes, FTY720 protects against pancreatic islet cell infiltration. Jörns et al. used one of these—a rat model of T1DM, the LEW.1AR1 (IDDM rat)—to identify changes in immune cells and lymph nodes associated with the pancreas in IDDM rats treated with FTY720.

The researchers treated IDDM rats with FTY720 before any signs of diabetes were apparent, and then divided the animals into groups that either did or did not show immune cell activation. Two additional groups of rats were either nondiabetic or diabetic and were not treated with FTY720. The authors found that treatment with FTY720 delayed T1DM development for 60 days beyond the usual time of diabetes onset in IDDM rats and that diabetes was prevented for 30 days after the last FTY720 treatment. Notably, immune cells remained active, as measured by gene and inflammatory cytokine expression. They concluded that FTY720 treatment prevented T1DM development while still maintaining immune cell activation in lymph nodes.

This study is an exciting illustration of the use of an established therapeutic agent, in this case for prevention of organ transplant rejection and other autoimmune inflammatory diseases, that may have an important use for the prevention of another disease: type 1 diabetes. Adding to its appeal, this therapy has no severe adverse effects at the dose at which it prevents diabetes in rats, demonstrating its promise for further human study.

A. Jörns et al., Diabetes prevention by immunomodulatory FTY720 treatment in the LEW.1AR1-iddm rat despite immune cell activation. Endocrinology 151, 3555–3565 (2010). [Abstract]

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